Laboratory of Rheumatology, GIGA-Research, CHULiège, ULiège, 4000, Liège, Belgium.
Department of Orthopaedic Surgery, CHULiège, 4000, Liège, Belgium.
Cell Mol Life Sci. 2022 Apr 27;79(5):260. doi: 10.1007/s00018-022-04282-6.
Osteoarthritis (OA) synovial membrane is mainly characterized by low-grade inflammation, hyperplasia with increased cell proliferation and fibrosis. We previously underscored a critical role for CEMIP in fibrosis of OA cartilage. However, its role in OA synovial membrane remains unknown. An in vitro model with fibroblast-like synoviocytes from OA patients and an in vivo model with collagenase-induced OA mice were used to evaluate CEMIP-silencing effects on inflammation, hyperplasia and fibrosis. Our results showed that i. CEMIP expression was increased in human and mouse inflamed synovial membrane; ii. CEMIP regulated the inflammatory response pathway and inflammatory cytokines production in vitro and in vivo; iii. CEMIP induced epithelial to mesenchymal transition pathway and fibrotic markers in vitro and in vivo; iv. CEMIP increased cell proliferation and synovial hyperplasia; v. CEMIP expression was increased by inflammatory cytokines and by TGF-β signaling; vi. anti-fibrotic drugs decreased CEMIP expression. All these findings highlighted the central role of CEMIP in OA synovial membrane development and underscored that targeting CEMIP could be a new therapeutic approach.
骨关节炎（OA）滑膜主要以低度炎症、增生伴有细胞增殖增加和纤维化。我们之前强调了 CEMIP 在 OA 软骨纤维化中的关键作用。然而，其在 OA 滑膜中的作用尚不清楚。我们使用来自 OA 患者的成纤维细胞样滑膜细胞的体外模型和胶原酶诱导的 OA 小鼠的体内模型来评估 CEMIP 沉默对炎症、增生和纤维化的影响。我们的结果表明：i. CEMIP 在人和小鼠炎症滑膜中表达增加；ii. CEMIP 调节体外和体内炎症反应途径和炎症细胞因子的产生；iii. CEMIP 在体外和体内诱导上皮到间充质转化途径和纤维化标志物；iv. CEMIP 增加细胞增殖和滑膜增生；v. 炎症细胞因子和 TGF-β 信号通路增加 CEMIP 的表达；vi. 抗纤维化药物降低 CEMIP 的表达。所有这些发现都强调了 CEMIP 在 OA 滑膜发生发展中的核心作用，并强调了靶向 CEMIP 可能是一种新的治疗方法。
